Normal cellular metabolism is associated with the production of reactive oxygen species (ROS) and, as a consequence, damage to DNA and proteins. ROS have been implicated as signaling molecules that contribute to neurodegenerative diseases and aging. The generation of ROS is associated with apoptosis and certain cells, particularly neurons, are highly sensitive to this response. Studies have indicated that ROS-induced apoptosis is p53-dependent and that p53-induced apoptosis is mediated by ROS. In addition, the p66shc adaptor protein and the p85 subunit of phosphatidylinositol 3-kinase (PI3-K) have been implicated in the apoptotic response to oxidative stress.
Antioxidants have been proposed as one approach to diminish ROS damage to cells. Importantly, the signaling pathways responsible for ROS-induced apoptosis are for the most part unknown.